What is the safest way to transition a patient from apixaban (Eliquis) to warfarin, including overlap timing, INR monitoring schedule, and bridging with low‑molecular‑weight heparin in renal impairment?

Transitioning from Apixaban (Eliquis) to Warfarin

Standard Transition Protocol

The FDA-approved method for switching from apixaban to warfarin requires discontinuing apixaban and simultaneously starting both a parenteral anticoagulant (typically enoxaparin) and warfarin at the time of the next scheduled apixaban dose, continuing the parenteral agent until the INR reaches therapeutic range (2.0-3.0) for two consecutive measurements. 1

Step-by-Step Transition Algorithm

Discontinue apixaban at the time of the next scheduled dose—do not give that dose 1

Immediately initiate both agents:

• Start warfarin at 5 mg daily (or 10 mg in healthy outpatients <60 years; 5 mg in elderly, hospitalized, or malnourished patients) 2
• Start therapeutic-dose enoxaparin: 1 mg/kg subcutaneously every 12 hours OR 1.5 mg/kg once daily 2, 3

Overlap duration:

• Continue both warfarin and enoxaparin for a minimum of 5-7 days 3
• Do not stop enoxaparin until INR is 2.0-3.0 on two consecutive measurements taken at least 24 hours apart 3, 4

INR Monitoring Schedule During Transition

Daily INR monitoring is mandatory starting from day 1 of warfarin initiation until the INR reaches and maintains therapeutic range for 2 consecutive days 3

After discontinuing enoxaparin, check INR 2-3 times weekly for the first 1-2 weeks, then weekly for the first month, then monthly once stable 3, 5

Critical Pitfall: Apixaban's Effect on INR

Apixaban artificially elevates the INR, making initial INR measurements unreliable for determining appropriate warfarin dosing during the transition 1, 6. This is why the FDA mandates parenteral bridging rather than relying on INR alone—the INR may appear therapeutic while apixaban is still present, but warfarin has not yet achieved its full anticoagulant effect 1

Special Considerations in Renal Impairment

When to Avoid LMWH Bridging

In patients with severe renal impairment (creatinine clearance <30 mL/min), unfractionated heparin is preferred over enoxaparin because low-molecular-weight heparins undergo renal clearance and accumulate, increasing bleeding risk 7, 8

If enoxaparin must be used in moderate renal impairment (CrCl 30-50 mL/min), closer monitoring with anti-Factor Xa levels (target 0.3-0.7 IU/mL) may be warranted 2, 3

Apixaban Clearance in Renal Dysfunction

Apixaban exposure increases by only 44% even in severe renal impairment (CrCl 15 mL/min), and it does not require dose adjustment based on renal function alone 9. However, apixaban's prolonged half-life in renal dysfunction means it will continue to affect the INR for a longer period, complicating the transition 6

In patients with acute-on-chronic kidney disease, consider measuring chromogenic apixaban anti-Xa levels to confirm apixaban clearance before relying solely on INR for warfarin dosing 6. This approach can potentially avoid unnecessary prolonged parenteral anticoagulation 6

Alternative Bridging Strategy in Severe Renal Impairment

For patients with CrCl <30 mL/min:

• Discontinue apixaban
• Start warfarin 5 mg daily
• Start unfractionated heparin IV (80 units/kg bolus, then 18 units/kg/hour, adjusted by aPTT to 1.5-2.5× control) 7
• Continue heparin until INR is 2.0-3.0 for two consecutive days

Cancer Patients: A Critical Exception

In patients with active cancer and venous thromboembolism, do not transition to warfarin—continue apixaban or switch to therapeutic-dose enoxaparin for at least 6 months 4, 2. Low-molecular-weight heparin provides superior outcomes compared to warfarin in this population, with lower VTE recurrence rates 4, 2

If warfarin is absolutely required in a cancer patient (e.g., mechanical valve), use the standard bridging protocol but recognize these patients require particularly close monitoring due to higher rates of both thrombotic and bleeding complications 3

Common Errors to Avoid

Never stop apixaban and start warfarin alone without bridging anticoagulation—this creates a period of subtherapeutic anticoagulation because warfarin requires 5-7 days to achieve full effect 1

Do not confuse prophylactic enoxaparin doses (40 mg daily) with therapeutic bridging doses (1 mg/kg every 12 hours or 1.5 mg/kg daily)—underdosing leaves the patient unprotected 2

Do not discontinue enoxaparin based on a single therapeutic INR—require two consecutive therapeutic measurements at least 24 hours apart to ensure warfarin has achieved stable anticoagulation 3, 4

Do not use therapeutic-dose LMWH in severe renal impairment (CrCl <30 mL/min) without anti-Xa monitoring or switch to unfractionated heparin 7, 8